Zinc adjuvant treatment in SARS-CoV-2: A randomized clinical trial
Silvia Gómez-Zorrilla, Elena Sendra, Juan Du, Mercé Espona, Alejandro Fierro-Villegas, Ana Siverio, Alicia Rodriguez-Alarcón, Silvia Castañeda, Inmaculada López Montesinos, Cristina Plata, Itziar Arrieta-Aldea, Jade Soldado-Folgado, Natalia García-Giralt, Rubén Vicente, Robert Güerri-Fernández
Journal of Trace Elements in Medicine and Biology, doi:10.1016/j.jtemb.2025.127778
Introduction: Zinc is a trace element with a key role in immune function and has demonstrated antiviral and antiinflammatory properties. Low plasma zinc levels have been associated with poor outcomes in COVID-19. This study aims to evaluate the efficacy and safety of zinc supplementation as an adjuvant therapy in hospitalized patients with COVID-19. Methods: A single-center, randomized, open-label clinical trial between May and December 2021. Adults hospitalized with confirmed COVID-19 requiring hospitalization were randomized 1:1 to receive standard of care (SoC) with or without oral zinc acetate (90 mg/day) for 14 days. The primary endpoint was disease progression, defined as critical care requirement (ICU admission) or death. Secondary outcomes included time to clinical recovery, hospital length of stay, WHO clinical scale improvement, inflammatory markers, antibody response, and safety. Results: Seventy-one patients were randomized (35 zinc versus 34 SoC). Disease progression occurred in 5.7 % of the zinc group versus 23.5 % in the SoC group (OR 0.21, 95 %CI = 0.03-0.96,). Mean recovery time was significantly shorter in the zinc group (7.4 ± 6.1 versus 13.1 ± 9.7 days, p = 0.006) and a trend to a faster recovery was observed in the Cox proportional hazards model in the intervention group HR of 1.670 (95 % CI: 0.948-2.942), p = 0.076. WHO scale improvement attaining a < 1 points at day 14 was greater in the zinc group (74.3 % versus 42.4 %, p = 0.009). Antibody levels were higher in the SoC group at days 14 and 28. No adverse events were attributed to zinc. Conclusions: Adjunctive zinc supplementation to standard of care reduced disease progression and showed a trend to accelerated clinical recovery in hospitalized COVID-19 patients, supporting the potential role of zinc in managing viral respiratory infections.
Declaration of Competing Interest None of the authors have a conflict of interest to disclose.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at doi:10.1016/j.jtemb.2025.127778.
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